15.5.2. Arboviruses

Viruses which multiply in an invertebrate vector and a vertebrate host are termed arboviruses. This definition excludes the mechanically transmitted viruses, such as the myxoma virus that causes myxomatosis in rabbits. There is no viral amplification in myxomatosis vectors such as the rabbit flea, Spilopsyllus cuniculi, and, in Australia, Anopheles and Aedes mosquitoes. Arboviruses are united by their ecologies, notably their ability to replicate in an arthropod. It is an unnatural grouping rather than one based upon virus phylogeny, as arboviruses belong to several virus families. These include some Bunyaviridae, Reoviridae, and Rhabdoviridae, and notably many Flaviviridae and Togaviridae. Alphavirus (Togaviridae) includes exclusively mosquito-transmitted viruses, notably the agents of equine encephalitides. Members of Flavivirus (Flaviviridae), which includes yellow fever, dengue, Japanese encephalitis, West Nile, and other encephalitis viruses, are borne by mosquitoes or ticks.

Yellow fever exemplifies a flavivirus life cycle. A similar cycle to the African sylvan (forest) one seen in section 15.4 involves a primate host in Central and South America, although with different mosquito vectors from those in Africa. Sylvan transmission to humans does occur, as in Ugandan banana plantations, but the disease makes its greatest fatal impact in urban epidemics. The urban and peridomestic insect vector in Africa and the Americas is the female of the yellow- fever mosquito, Aedes (Stegomyia) aegypti. This mosquito acquires the virus by feeding on a human yellow-fever sufferer in the early stages of disease, from 6 h preclinical to four days later. The viral cycle in the mosquito is 12 days long, after which the yellow-fever virus reaches the mosquito saliva and remains there for the rest of the mosquito’s life. With every subsequent blood meal the female mosquito transmits virus-contaminated saliva. Infection results, and yellow-fever symptoms develop in the host within a week. An urban disease cycle must originate from individuals infected with yellow fever from the sylvan (rural) cycle moving to an urban environment. Here, disease outbreaks may persist, such as those in which hundreds or thousands of people have died, including in New Orleans as recently as 1905. In South America, monkeys may die of yellow fever, but African ones are asymptomatic: perhaps neotropical monkeys have yet to develop tolerance to the disease. The common urban mosquito vector, Ae. aegypti, may have been transported relatively recently from West Africa to South America, perhaps aboard slave ships, together with yellow fever. The range of Ae. aegypti is greater than that of the disease, being present in southern USA, where it is spreading, and in Australia, and much of Asia. However, only in India are there susceptible but, as yet, uninfected monkey hosts of the disease.

Other Flaviviridae affecting humans and transmitted by mosquitoes cause dengue, dengue hemorrhagic fever, and a number of diseases called encephalitis (or encephalitides), because in clinical cases inflammation of the brain occurs. Each encephalitis has a preferred mosquito host, frequently an Aedes (Stegomyia) species such as Ae. aegypti for dengue, and often a Culex species for encephalitis. The reservoir hosts for these diseases vary, and, at least for encephalitis, include wild birds, with amplification cycles in domestic mammals, for example pigs for Japanese encephalitis. Horses can be carriers of togaviruses, giving rise to the name for a subgroup of diseases termed “equine encephalitides”.

West Nile virus belongs to the Japanese encephalitis virus complex, preferentially transmitted by Culex species, with wild birds as reservoirs able to amplify the virus during outbreaks. The virus is distributed widely from the western Mediterranean eastward through the Middle East, Africa to India and Indonesia. Human symptoms and mortality vary with age, health, and virus strain, but encephalitis is uncommon. The disease entered New York from an unknown source in 1999, causing seven human deaths from 61 confirmed cases (and many more asymptomatic infections), and the mortality of many wild birds, especially Corvus species (crows). In subsequent years the geographic distribution has spread rapidly south and westward and reached the Pacific coast states of the USA in 2003. Many wild birds and more humans have died, and the range of potential vector mosquitoes has expanded beyond the species of Culex identified in New York. As in some European outbreaks, horses have proved susceptible and a vaccine has become available.

Several flaviviruses are transmitted by ixodid ticks, including more viruses that cause encephalitis and hemorrhagic fevers of humans, but more significantly of domestic animals. Bunyaviruses may be tick-borne, notably hemorrhagic diseases of cattle and sheep, particularly when conditions encourage an explosion of tick numbers and disease alters from normal hosts (enzootic) to epidemic (epizootic) conditions. Mosquito-borne bunyaviruses include African Rift Valley fever, which can produce high mortality amongst African sheep and cattle during mass outbreaks.

Amongst the Reoviridae, bluetongue virus is the best known, most debilitating, and most significant economically. The disease, which is virtually world-wide and has many different serotypes, causes tongue ulceration (hence “bluetongue”) and an often terminal fever in sheep. Bluetongue is one of the few diseases in which biting midges of Culicoides (Ceratopogonidae) have been clearly established as the sole vectors of an arbovirus of major significance, although many arboviruses have been isolated from these biting flies.

Studies of the epidemiology of arboviruses have been complicated by the discovery that some viruses may persist between generations of vector. Thus, La Crosse virus, a bunyavirus that causes encephalitis in the USA, can pass from the adult mosquito through the egg (transovarial transmission) to the larva, which over-winters in a near-frozen tree-hole. The first emerging female of the spring generation is capable of transmitting La Crosse virus to chipmunk, squirrel, or human with her first meal of the year. Transovarial transmission is suspected in other diseases and is substantiated in increasing numbers of cases, including Japanese encephalitis in Culex tritaenorhynchus mosquitoes.